Human liver is an estrogen-responsive organ. For example, it increases synthesis of transport proteins and alters drug metabolism and excretion when exposed to estrogen. Such estrogen responsiveness suggests the presence of estrogen receptors, cytosolic proteins that mediate the response between hepatocyte and sex hormone. In fact, we have demonstrated the presence of estrogen receptor in normal human liver from both sexes. We now propose to examine liver-estrogen interactions in a variety of human liver diseases. In preliminary studies, we have observed that women with oral contraceptive-associated liver disease and rats chronically fed alcohol have unique alterations in hepatic estrogen receptor content compared to that in normal tissue. In addition, we are particularly interested in the effect such alterations in hepatic estrogen receptor may have on the feminization seen in alcoholic men. Therefore, we propose to: 1. Characterize and quantitate estrogen receptor in diseased human liver and compare the findings to those obtained using appropriate controls; 2. Develop a microassay for quantitation of estrogen receptor in liver biopsysized pieces of human liver; 3. Correlate estrogen receptor activity with the plasma levels of liver enzymes, sex hormones, sex-steroid binding globulin and liver histopathology; 4. Compare the factors defined above in #3 with the degree of feminization observed clinically in alcoholic men.